The invention relates to medical systems and, more particularly, to non-invasive application of focused ultrasound energy to subjects such as humans, and in particular to the brain of a human subject.
Treatment of tissues lying at specific locations within the skull may be limited to removal or ablation. While these treatments have proven effective for certain localized disorders, such as tumors, they involve delicate, time-consuming procedures that may result in destruction of otherwise healthy tissues. These treatments are generally not appropriate for disorders in which diseased tissue is integrated into healthy tissue, except in instances where destruction of the healthy tissue will not unduly effect neurologic function.
The noninvasive nature of ultrasound surgery has special appeal in the brain where it is often desirable to destroy or treat deep tissue volumes without disturbing healthy tissues. Focused ultrasound beams have been used for noninvasive surgery in many other parts of the body. Ultrasound penetrates well through soft tissues and, due to the short wavelengths (1.5 mm at 1 MHz), it can be focused to spots with dimensions of a few millimeters. By heating, e.g., using ultrasound, tumorous or cancerous tissue in the abdomen, for example, it is possible to ablate the diseased portions without significant damage to surrounding healthy tissue.
In general, in one aspect, the invention provides a method of delivering ultrasound signals. The method includes providing an image of at least a portion of a subject intended to receive ultrasound signals between sources of the ultrasound signals and a desired region of the subject for receiving focused ultrasound signals, identifying, from the image, physical characteristics of different layers of material between the sources and the desired region, and determining at least one of phase corrections and amplitude corrections for the sources depending on respective thicknesses of portions of each of the layers disposed between each source and the desired region.
Implementations of the invention may include one or more of the following features. The physical characteristics are associated with material type and at least one of material density and material structure, the identifying further comprising identifying thicknesses of the layers. The phase corrections are determined in accordance with propagation characteristics of each of the layers. The propagation characteristics are determined based upon the material type and at least one of the material density and the material structure of each of the respective layers. The layers are identified using values associated with portions of the image. The values are intensities of the portions of the image. The phase corrections are determined using a three-layer model of a skull of the subject. Two of the three layers are assumed to have approximately identical speeds of sound, ci, therein, with the other layer having a speed of sound cii therein, wherein the phase corrections are determined using a phase shift determined according to:   φ  =      360    ⁢    f    ⁢                  ∑                  n          =          1                3            ⁢              xe2x80x83            ⁢                        D          n                ⁡                  (                                    1                              c                0                                      -                          1                              c                n                                              )                    
where cn is a speed of sound in the nth layer, and Dn is a thickness of the nth layer, and wherein the speeds of sound in the layers are determined according to:             c      i        ⁡          (      ρ      )        =                    (                              d            1                    +                      d            3                          )            ⁡              [                                                            d                1                            +                              d                2                            +                              d                3                                                    c              0                                -                                    d              2                                      c              ii                                -                                    φ              ⁡                              (                ρ                )                                                    360              ⁢              fD                                      ]                    -      1      
where d1, d2, d3, are thicknesses of the three layers, xcfx86(xcfx81) is a measured phase shift as a function of density, and xcfx81 is density.
Further, implementations of the invention may include one or more of the following features. The physical characteristics are associated with x-ray attenuation coefficients, xcexc. The material between the sources and the desired region is bone. The phase corrections are related to the attenuation coefficient by a phase function including parameters derived at least partially experimentally. Each phase correction equals M+Bxcexa3(1/xcexc(x))+Cxcexa3(1/xcexc(x))2, where xcexc(x) is the attenuation coefficient as a function of distance x along a line of propagation between each source and the desired region, and where M, B, and C are derived at least partially experimentally. The amplitude corrections are related to the attenuation coefficient by an amplitude function including parameters derived at least partially experimentally. Each amplitude correction is related to N+Fxcexa3xcexc(x)+Gxcexa3(xcexc(x))2, where xcexc(x) is the attenuation coefficient as a function of distance x along a line of propagation between each source and the desired region, and where N, F, and G are derived at least partially experimentally.
Further, implementations of the invention may include one or more of the following features. The layers are identified according to both material density and material structure. Providing the image includes producing the image using magnetic resonance imaging. Providing the image includes producing the image using computer tomography. The sources are piezoelectric transducer elements. Both phase and amplitude corrections are determined.
In general, in another aspect, the invention provides a system for delivering ultrasound signals. The system includes an apparatus configured to analyze an image of at least a portion of a subject intended to receive ultrasound signals between sources of the ultrasound signals and a desired region of the subject for receiving focused ultrasound signals, the apparatus configured to determine, from the image, information about different layers of the at least a portion of the subject, and an array of sources of ultrasound signals having at least one of their relative phases and their amplitudes set in accordance with the information about each layer of the at least a portion of the subject provided by the apparatus.
Implementations of the invention may include one or more of the following features. The phases are set in accordance with propagation characteristics of each layer of the at least a portion of the subject. The propagation characteristics are dependent upon the material type and at least one of the material density and the material structure of each layer of the at least a portion of the subject. The apparatus is configured to identify the layers using values associated with portions of the image. The values are intensities of the portions of the image. The apparatus is configured to determine the information about different layers of bone. The apparatus is configured to determine the phase corrections using a three-layer model of a skull of the subject. The information is associated with an x-ray attenuation coefficient, xcexc. The phase corrections are related to the attenuation coefficient by a phase function including parameters derived at least partially experimentally. The amplitude corrections are related to the attenuation coefficient by an amplitude function including parameters derived at least partially experimentally.
Further, implementations of the invention may include one or more of the following features. The system further includes a magnetic resonance imager coupled to the apparatus and configured to produce the image. The system further includes a computer tomography imager coupled to the apparatus and configured to produce the image. The sources are piezoelectric transducer elements.
In general, in another aspect, the invention provides a computer program product residing on a computer readable medium and comprising instructions for causing a computer to analyze an image of at least a portion of a subject to receive ultrasound signals between sources of the ultrasound signals and a desired region of the subject for receiving focused ultrasound signals to identify, from the image, physical characteristics of layers of material between the sources and the desired region, and to determine at least one of phase corrections and amplitude corrections for the sources depending on respective thicknesses of portions of each of the layers disposed between each source and the desired region.
Implementations of the invention may include one or more of the following features. The phase corrections are determined in accordance with propagation characteristics of each of the layers. The propagation characteristics are dependent upon the material type and at least one of the material density and the material structure of each of the respective layers. The layers are identified according to both material density and material structure. The computer program product further includes instructions for causing a computer to produce the image using magnetic resonance imaging. The computer program product further includes instructions for causing a computer to produce the image using computer tomography. The instructions for causing a computer to identify layers of materials are for causing the computer to identify the layers of materials based upon intensities of portions of the image.
Further, implementations of the invention may include one or more of the following features. The layers are identified using values associated with portions of the image. The values are intensities of the portions of the image. The layers analyzed are layers of bone. The phase corrections are determined using a three-layer model of a skull of the subject. Two of the three layers are assumed to have approximately the same speed of sound, ci, therein, with the other layer having a speed of sound cii therein, wherein the phase corrections are determined using a phase shift determined according to:   φ  =      360    ⁢    f    ⁢                  ∑                  n          =          1                3            ⁢              xe2x80x83            ⁢                        D          n                ⁡                  (                                    1                              c                0                                      -                          1                              c                n                                              )                    
where cn is a speed of sound in the nth layer, and Dn is a thickness of the nth layer, and wherein the speeds of sound in the layers are determined according to:             c      i        ⁡          (      ρ      )        =                    (                              d            1                    +                      d            3                          )            ⁡              [                                                            d                1                            +                              d                2                            +                              d                3                                                    c              0                                -                                    d              2                                      c              ii                                -                                    φ              ⁡                              (                ρ                )                                                    360              ⁢              fD                                      ]                    -      1      
where d1, d2, d3, are thicknesses of the three layers, xcfx86(xcfx81) is a measured phase shift as a function of density, and xcfx81 is density.
Further, implementations of the invention may include one or more of the following features. The physical characteristics are associated with x-ray attenuation coefficients, xcexc. The phase corrections are related to the attenuation coefficient by a phase function including parameters derived at least partially experimentally. Each phase correction equals M+Bxcexa3(1/xcexc(x))+Cxcexa3(1/xcexc(x))2, where xcexc(x) is the attenuation coefficient as a function of distance x along a line of propagation between each source and the desired region, and where M, B, and C are derived at least partially experimentally. The amplitude corrections are related to the attenuation coefficient by an amplitude function including parameters derived at least partially experimentally. Each amplitude correction is related to N+Fxcexa3xcexc(x)+Gxcexa3(xcexc(x))2, where xcexc(x) is the attenuation coefficient as a function of distance x along a line of propagation between each source and the desired region, and where N, F, and G are derived at least partially experimentally.
In general, in another aspect, the invention provides a method of providing ultrasound signals into a subject from at least one source of an array of sources of ultrasound signals. The method includes (a) transmitting ultrasound energy of a selected frequency from a selected source into the subject, (b) receiving superimposed reflections of the transmitted energy, the reflections being from an outer surface of the subject and at least one interface inside the subject, (c) repeating (a) and (b) using ultrasound energy of frequencies other than the selected frequency, (d) determining a frequency difference between frequencies associated with relative extrema of the received reflections, and (e) using the determined frequency difference and a thickness, of at least a portion of material between the selected source and a desired region in the subject for receiving focused ultrasound energy signals, to determine a phase correction for the selected source.
Implementations of the invention may include one or more of the following features. The method further includes (f) providing an image of at least a portion of a subject intended to receive ultrasound energy signals between sources of the energy signals and the desired region, and (g) identifying, from the image, the thickness of at least a portion of material between the selected source and the desired region. The method further includes repeating (a)-(e) for each of the sources other than the selected source. The phase correction is determined according to:
xcex94xcfx86=2xcfx80f[(d/c0)xe2x88x92(1/(2xcex94f))]
where xcex94xcfx86 is the phase correction, f is a frequency to be transmitted, d is the thickness, c0 is the speed of sound in water, and xcex94f is the frequency difference between like extrema.
In general, in another aspect, the invention provides logic for use in a system for providing ultrasound energy into a living subject from an array of sources of ultrasound energy signals. The logic is configured to control apparatus to (a) transmit ultrasound energy of a selected frequency from a selected source into the subject, (b) receive superimposed reflections of the transmitted energy, the reflections being from an outer surface of the subject and at least one interface inside the subject, (c) repeat (a) and (b) using ultrasound energy of frequencies other than the selected frequency, (d) determine a frequency difference between frequencies associated with relative extrema of the received reflections, and (e) use the determined frequency difference and a thickness, of at least a portion of material between the selected source and a desired region in the subject for receiving focused ultrasound energy signals, to determine a phase correction for the selected source.
Implementations of the invention may include one or more of the following features. The logic is further configured to cause the apparatus to (f) provide an image of at least a portion of a subject intended to receive ultrasound energy signals between sources of the energy signals and the desired region, and (g) identify, from the image, the thickness of at least a portion of material between the selected source and the desired region. The logic is further configured to cause the apparatus to repeat (a)-(e) for each of the sources other than the selected source. The logic is configured to cause the apparatus to determine the phase correction according to:
xcex94xcfx86=2xcfx80f[(d/c0)xe2x88x92(1/(2xcex94f))]
where xcex94xcfx86 is the phase correction, f is a frequency to be transmitted, d is the thickness, c0 is the speed of sound in water, and xcex94f is the frequency difference between like extrema.
Various aspects of the invention may provide one or more of the following advantages. Ultrasound can be focused accurately within an intact skull, e.g., for ultrasound therapy. Different skulls, e.g., different skull thicknesses, densities, and/or structures, can be accommodated for ultrasound therapy. Real-time adjustments to ultrasound therapy can be made. Effects on phase and/or amplitude of energy passing through bone (or other tissue) may be determined and used to compensate the phase and/or amplitude of energy applied to the bone (or other tissue).
These and other advantages of the invention, along with the invention itself, will be more fully understood after a review of the following figures, detailed description, and claims.